Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy.

OBJECTIVES: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

Copeptin as a prognostic biomarker in acute myocardial infarction.

BACKGROUND: Copeptin - the C-terminal section of vasopressin precursor - is a novel biomarker, that has been shown to be a useful prognostic factor in heart failure, ischemic stroke and in acute myocardial infarction (MI) but with restricted population and follow-up in ST-segment elevation MI (STEMI) setting. We evaluated in this study the hypothesis that copeptin measured on admission is an independent predictor of one-year all-cause mortality after a STEMI. METHODS: Copeptin was measured immediately on arrival in the catheterization laboratory in a cohort of unselected STEMI patients and was compared to the peak of cardiac troponin I as a prognosis marker. One-year follow-up was performed. RESULTS: We included 401 STEMI patients (77% of men, mean age 64 ±â€¯14 years) treated by primary percutaneous coronary intervention. Copeptin on admission was significantly higher in patients who died during the one-year follow-up than in survivors (154.8 pmol/L; IQR [63.9-304.8] vs 30.3 pmol/L; IQR [10.8-93.5]); p < 0.0001). There was an increase in mortality at one year from the lowest to the highest quartile of copeptin. After Cox regression analysis, copeptin was an independent predictor of death at one year (adjHR 3.1, 95% CI [1.5-6.2], p = 0.001). When compared to the peak value of cardiac troponin I, copeptin measured on admission had a better prognostic value to predict one-year mortality (AUC of 0.74 vs 0.60, p = 0.022). CONCLUSION: Copeptin measured on admission is a reliable and independent prognostic biomarker of one-year mortality in acute myocardial infarction patients.

Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

Wide-range CRP versus high-sensitivity CRP on Roche analyzers: focus on low-grade inflammation ranges and high-sensitivity cardiac troponin T levels.

Wide-range C-reactive protein (wr-CRP) has been proposed as an economical alternative to high-sensitivity C-reactive protein (hs-CRP) for the evaluation of low-grade inflammation-associated cardiovascular risk (LGI-CVR). Concomitant values of serum hs-CRP and plasma wr-CRP ≤5 mg/L, and high-sensitivity cardiac troponin T (hs-cTnT), all assayed on Roche Diagnostics analyzers over a 1.8-year period, were extracted from a hospital laboratory database. Hs-CRP and wr-CRP values were compared (Bland-Altman method; Deming's correlation), then separately classified into low (<1 mg/L), moderate (1-3 mg/L) and high (>3 mg/L) LGI-CVR ranges for agreement test (κ), assessed before and after Deming's regression-based adjustment of wr-CRP (Adj-wr-CRP). Wr-CRP and hs-CRP values were strongly correlated, with linearity, whether below 5 mg/L (n = 744; τ = 0.933; p < .001) or below 1 mg/L (n = 283; τ = 0.823; p < .001). Overall, wr-CRP values were lower than hs-CRP (mean bias: -0.11 ± 0.17 mg/L). Agreement was good, with 8.1% of wr-CRP values misclassified compared to hs-CRP (κ: 0.874), and weakly improved after regression-based adjustment (7.7% reclassified values; κ: 0.881). Lowering the Adj-wr-CRP cutoff of the moderate LGI-CVR subrange from 1.0 to 0.9 mg/L resulted in an almost perfect agreement (3.2% reclassified data; κ: 0.950). Hs-cTnT concentration was positively associated with hs-CRP, wr-CRP, and Adj-wr-CRP (p < .001). Within each LGI-CVR subrange, hs-cTnT medians were similar regardless of the hs-CRP, wr-CRP or Adj-wr-CRP used for risk classification. Based on hs-cTnT, this study supports the use of wr-CRP as a low-cost alternative to hs-CRP for cardiovascular risk evaluation.

Mid-regional pro-adrenomedullin and copeptin to predict short-term prognosis of COPD exacerbations: a multicenter prospective blinded study.

BACKGROUND: Exacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes. PATIENTS AND METHODS: This prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit. RESULTS: A total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77-1.48) versus 0.83 nmol/L (0.63-1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57-0.89), 0.83 nmol/L (0.62-1.12) and 0.95 nmol/L (0.75-1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10-2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%-58%) and a specificity of 79% (95% CI, 74-84). CONCLUSION: MR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short-term outcomes.

Elevated procalcitonin is associated with bacterial infection during acute liver failure only when unrelated to acetaminophen intoxication.

AIM: The aim of this study was to evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection and survival without transplantation upon admission in the ICU for acute liver failure (ALF). PATIENTS AND METHODS: From January 2009 until October 2015, all cases of ALF patients admitted in our ICU were retrospectively reviewed and included in the study if the PCT level upon admission was available. Patients with pre-existing liver pathology or ALF in a context of already advanced multiorgan failure were excluded. The main clinical and biological characteristics of patients were recorded, as well as the etiology of ALF, diagnosis of bacterial infection (bacteriologically documented or suspected), and outcome. RESULTS: 35 patients were included: 46% men, mean age 42 years, initial prothrombin ratio 31%, PCT 9.8 mg/l (0.7-49), and PCT more than 2 mg/l in 54% of cases. Etiology was acetaminophen intoxication in 18/35 (51%) cases. Sepsis was diagnosed in 9/35 (26%) cases, most frequently pneumonia with 4/9 cases. Survival without liver transplantation (LT) was observed in 28 (80%) cases. The median PCT was not different in patients with or without bacterial infection [6.3 mg/l (0.6-16) vs. 1.2 mg/l (0.8-9.7), P=0.8]. The median PCT was not different in patients who survived without LT [7.1 mg/l (0.9-16.1) vs. 0.75 mg/l (7.7-11.5), P=0.06]. In patients with ALF unrelated to acetaminophen intoxication, the median PCT was higher in patients with bacterial infection [1.1 mg/l (0.9-4) vs. 0.5 mg/l (0.3-0.8), P=0.01], but was similar in patients who did not survive without LT [0.7 mg/l (0.4-1.1) vs. 0.8 mg/l (0.4-2.2), P=0.6]. In the overall cohort, the median C-reactive protein (CRP) and leukocyte count were higher in patients who developed bacterial infection [40 mg/l (19-60) vs. 16 mg/l (6-34), P=0.04; 11.9 G/l (8.3-19) vs. 7.9 G/l (6-12.6), P=0.05]. The median CRP and leukocyte count were not significantly different in survivors versus nonsurvivors without LT. CONCLUSION: PCT was an accurate predictor for the diagnosis of bacterial infection only in patients with ALF unrelated to acetaminophen intoxication. CRP was higher in patients who developed infection and could also be an interesting tool in ALF patients.

The TRIAGE-ProADM Score for an Early Risk Stratification of Medical Patients in the Emergency Department - Development Based on a Multi-National, Prospective, Observational Study.

INTRODUCTION: The inflammatory biomarker pro-adrenomedullin (ProADM) provides additional prognostic information for the risk stratification of general medical emergency department (ED) patients. The aim of this analysis was to develop a triage algorithm for improved prognostication and later use in an interventional trial. METHODS: We used data from the multi-national, prospective, observational TRIAGE trial including consecutive medical ED patients from Switzerland, France and the United States. We investigated triage effects when adding ProADM at two established cut-offs to a five-level ED triage score with respect to adverse clinical outcome. RESULTS: Mortality in the 6586 ED patients showed a step-wise, 25-fold increase from 0.6% to 4.5% and 15.4%, respectively, at the two ProADM cut-offs (≤0.75nmol/L, >0.75-1.5nmol/L, >1.5nmol/L, p ANOVA <0.0001). Risk stratification by combining ProADM within cut-off groups and the triage score resulted in the identification of 1662 patients (25.2% of the population) at a very low risk of mortality (0.3%, n = 5) and 425 patients (6.5% of the population) at very high risk of mortality (19.3%, n = 82). Risk estimation by using ProADM and the triage score from a logistic regression model allowed for a more accurate risk estimation in the whole population with a classification of 3255 patients (49.4% of the population) in the low risk group (0.3% mortality, n = 9) and 1673 (25.4% of the population) in the high-risk group (15.1% mortality, n = 252). CONCLUSIONS: Within this large international multicenter study, a combined triage score based on ProADM and established triage scores allowed a more accurate mortality risk discrimination. The TRIAGE-ProADM score improved identification of both patients at the highest risk of mortality who may benefit from early therapeutic interventions (rule in), and low risk patients where deferred treatment without negatively affecting outcome may be possible (rule out).

Droplet digital PCR of circulating tumor cells from colorectal cancer patients can predict KRAS mutations before surgery.

In colorectal cancer (CRC), KRAS mutations are a strong negative predictor for treatment with the EGFR-targeted antibodies cetuximab and panitumumab. Since it can be difficult to obtain appropriate tumor tissues for KRAS genotyping, alternative methods are required. Circulating tumor cells (CTCs) are believed to be representative of the tumor in real time. In this study we explored the capacity of a size-based device for capturing CTCs coupled with a multiplex KRAS screening assay using droplet digital PCR (ddPCR). We showed that it is possible to detect a mutant ratio of 0.05% and less than one KRAS mutant cell per mL total blood with ddPCR compared to about 0.5% and 50-75 cells for TaqMeltPCR and HRM. Next, CTCs were isolated from the blood of 35 patients with CRC at various stage of the disease. KRAS genotyping was successful for 86% (30/35) of samples with a KRAS codon 12/13 mutant ratio of 57% (17/30). In contrast, only one patient was identified as KRAS mutant when size-based isolation was combined with HRM or TaqMeltPCR. KRAS status was then determined for the 26 available formalin-fixed paraffin-embedded tumors using standard procedures. The concordance between the CTCs and the corresponding tumor tissues was 77% with a sensitivity of 83%. Taken together, the data presented here suggest that is feasible to detect KRAS mutations in CTCs from blood samples of CRC patients which are predictive for those found in the tumor. The minimal invasive nature of this procedure in combination with the high sensitivity of ddPCR might provide in the future an opportunity to monitor patients throughout the course of disease on multiple levels including early detection, prognosis, treatment and relapse as well as to obtain mechanistic insight with respect to tumor invasion and metastasis.

Predictors for Delayed Emergency Department Care in Medical Patients with Acute Infections - An International Prospective Observational Study.

INTRODUCTION: In overcrowded emergency department (ED) care, short time to start effective antibiotic treatment has been evidenced to improve infection-related clinical outcomes. Our objective was to study factors associated with delays in initial ED care within an international prospective medical ED patient population presenting with acute infections. METHODS: We report data from an international prospective observational cohort study including patients with a main diagnosis of infection from three tertiary care hospitals in Switzerland, France and the United States (US). We studied predictors for delays in starting antibiotic treatment by using multivariate regression analyses. RESULTS: Overall, 544 medical ED patients with a main diagnosis of acute infection and antibiotic treatment were included, mainly pneumonia (n = 218; 40.1%), urinary tract (n = 141; 25.9%), and gastrointestinal infections (n = 58; 10.7%). The overall median time to start antibiotic therapy was 214 minutes (95% CI: 199, 228), with a median length of ED stay (ED LOS) of 322 minutes (95% CI: 308, 335). We found large variations of time to start antibiotic treatment depending on hospital centre and type of infection. The diagnosis of a gastrointestinal infection was the most significant predictor for delay in antibiotic treatment (+119 minutes compared to patients with pneumonia; 95% CI: 58, 181; p<0.001). CONCLUSIONS: We found high variations in hospital ED performance in regard to start antibiotic treatment. The implementation of measures to reduce treatment times has the potential to improve patient care.

Comparison of LUMIPULSE(®) G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers.

BACKGROUND: Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse(®) G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor(®) (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular(®) Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9, and Cyfra 21-1. METHODS: A total of 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse(®) G1200 and either Kryptor(®) (for AFP) or Modular(®) (for the six other markers). RESULTS: The good precision of Lumipulse(®) G1200 assays was confirmed with CVs < 2.5% and < 5.0%, obtained, respectively, for within-run imprecision and intermediate imprecision (except for Cyfra 21-1: CV < 13%). For all markers, Lumipulse results were well correlated with Modular or Kryptor results (r ≥ 0.94). Concordance of results interpretation was > 95% and tumor marker kinetics were all similar. CONCLUSION: We confirmed the analytical performances of Lumipulse(®) tumor marker assays except for the CYFRA 21-1 assay for which performances were poor in this study. We noticed a few discrepancies for the CEA assay. Besides, values obtained for CA 19-9 were higher with Lumipulse leading to a bias (slope = 1.5). But for the four other tumor markers assays (PSA, AFP, CA 125, CA 15-3), the results were directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual substitution of one system by another.

Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.

BACKGROUND: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. METHODS: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. RESULTS: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 µg/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p<0.0001). CONCLUSIONS: This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

INTRODUCTION: Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. METHOD: We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). RESULTS: During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. CONCLUSIONS: Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Predictive value of S100-B and copeptin for outcomes following seizure: the BISTRO International Cohort Study.

OBJECTIVE: To evaluate the performance of S100-B protein and copeptin, in addition to clinical variables, in predicting outcomes of patients attending the emergency department (ED) following a seizure. METHODS: We prospectively included adult patients presented with an acute seizure, in four EDs in France and the United Kingdom. Participants were followed up for 28 days. The primary endpoint was a composite of seizure recurrence, all-cause mortality, hospitalization or rehospitalisation, or return visit in the ED within seven days. RESULTS: Among the 389 participants included in the analysis, 156 (40%) experienced the primary endpoint within seven days and 195 (54%) at 28 days. Mean levels of both S100-B (0.11 µg/l [95% CI 0.07-0.20] vs 0.09 µg/l [0.07-0.14]) and copeptin (23 pmol/l [9-104] vs 17 pmol/l [8-43]) were higher in participants meeting the primary endpoint. However, both biomarkers were poorly predictive of the primary outcome with a respective area under the receiving operator characteristic curve of 0.57 [0.51-0.64] and 0.59 [0.54-0.64]. Multivariable logistic regression analysis identified higher age (odds ratio [OR] 1.3 per decade [1.1-1.5]), provoked seizure (OR 4.93 [2.5-9.8]), complex partial seizure (OR 4.09 [1.8-9.1]) and first seizure (OR 1.83 [1.1-3.0]) as independent predictors of the primary outcome. A second regression analysis including the biomarkers showed no additional predictive benefit (S100-B OR 3.89 [0.80-18.9] copeptin OR 1 [1.00-1.00]). CONCLUSION: The plasma biomarkers S100-B and copeptin did not improve prediction of poor outcome following seizure. Higher age, a first seizure, a provoked seizure and a partial complex seizure are independently associated with adverse outcomes.

[Last updates about amniotic fluid embolism and a case report]. / L'embolie amniotique : données récentes et illustration.

Amniotic fluid embolism (AFE) is a rare complication of pregnancy, which, in France, is the second leading cause of maternal mortality. It results from the passage of amniotic fluid into the maternal circulation, but mechanisms leading to clinical signs are not yet clearly identified. After a literature review, we report on the case of a 34 years old patient occurred during labor. Laboratory tests were performed during acute phase to diagnose coagulopathy and to monitor vital parameters. Further laboratory tests were conducted to support the diagnosis: cytology, study of insulin-like growth factor-binding protein 1, tryptase and alpha-foetoprotein. Performances and place of these laboratory tests must be precised as no specific test can attest the diagnosis.

Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers.

OBJECTIVE: Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection. STUDY DESIGN: Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. RESULTS: The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free ß-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free ß-hCG detects 58% for 5% or 70% for 10%. CONCLUSION: Combining AFP and BPD with free ß-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.

Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection.

OBJECTIVE: To study the contribution of lactate and procalcitonin (PCT) serum measurements for the diagnosis and the risk-stratification of patients with suspected infection presenting to the ED. METHODS: Single-center one year observational study on 462 consecutive patients. Multivariate analysis to assess variables associated with sepsis, severe sepsis, septic shock and severe outcome. RESULTS: Multivariate analysis (Odds ratio [95% CI]), showed that PCT was the best independent variable to identify sepsis (3.98 [2.60-6.10]), while lactate was the best to diagnose severe sepsis (10.88 [6.51-18.19]). Patients with both lactate above 2 mmol·L(-1) and PCT above 0.8 ng·mL(-1) had an enhanced risk of severe outcome. CONCLUSIONS: the dosages of lactate and PCT are complementary for the diagnosis and risk-stratification of patients evaluated in the ED for suspected infection.

Usefulness of cardiac biomarkers to predict cardiac recovery in patients on extracorporeal membrane oxygenation support for refractory cardiogenic shock.

BACKGROUND: No prognostic markers of myocardial recovery in patients with refractory cardiogenic shock requiring circulatory support are known, but early identification of patients who will not recover might provide an opportunity to change the treatment strategy to improve outcome. Because N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin are prognostic markers in patients with cardiac failure, we hypothesized that, among patients with refractory cardiogenic shock of potentially reversible cause supported with extracorporeal membrane oxygenation (ECMO), the kinetics of these markers might help identify patients who would recover. METHODS: This was a prospective, observational, single-center study in a medical-surgical intensive care unit. Among 41 consecutive patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, 18 recovered and were successfully weaned off the machine. Blood N-terminal fragment of the B-type natriuretic peptide, troponin Ic, midregional fragment of the proatrial natriuretic peptide, proadrenomedullin, and copeptin concentrations were determined on days 1, 3, and 7 post-ECMO. RESULTS: Neither the absolute values of those biomarkers at days 1, 3, or 7 nor their kinetics during the first week differed between patients weaned or not. Areas under the receiver operating characteristic curves (95% confidence interval) of the day 1-to-day 3 biomarker changes for predicting cardiac recovery were 0.54 (0.36-0.71), 0.61 (0.43-0.78), 0.61 (0.42-0.77), 0.56 (0.38-0.73), and 0.61 (0.43-0.78), respectively. CONCLUSION: In patients with refractory cardiogenic shock of potentially reversible cause receiving ECMO support, early measurements of cardiac biomarkers are not useful for identifying those who would recover.

Implication of NADPH oxidases in the early inflammation process generated by cystic fibrosis cells.

In cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality. The aim of this study was to further investigate whether oxidative stress could be involved in the early inflammatory process associated with CF pathogenesis. We used a model of CFTR defective epithelial cell line (IB3-1) and its reconstituted CFTR control (S9) cell line cultured in various ionic conditions. This study showed that IB3-1 and S9 cells expressed the NADPH oxidases (NOXs) DUOX1/2 and NOX2 at the same level. Nevertheless, several parameters participating in oxidative stress (increased ROS production and apoptosis, decreased total thiol content) were observed in IB3-1 cells cultured in hypertonic environment as compared to S9 cells and were inhibited by diphenyleneiodonium (DPI), a well-known inhibitor of NOXs; besides, increased production of the proinflammatory cytokines IL-6 and IL-8 by IB3-1 cells was also inhibited by DPI as compared to S9 cells. Furthermore, calcium ionophore (A23187), which upregulates DUOX and NOX2 activities, strongly induced oxidative stress and IL-8 and IL-6 overexpression in IB3-1 cells. All these events were suppressed by DPI, supporting the involvement of NOXs in the oxidative stress, which can upregulate proinflammatory cytokine production by the airway CFTR-deficient cells and trigger early pulmonary inflammation in CF patients.

[Potential value of CA125 kinetic monitoring in the initial management of advanced epithelial ovarian cancer]. / Intérêt potentiel du suivi de cinétique du CA125 dans la prise en charge initiale des cancers épithéliaux de l'ovaire de stade avancé

Ovarian carcinoma is account for 4% of all women cancer deaths because of late diagnosis at advanced stage. During chemotherapy, survey includes repeated assays of antigen carbohydrate 125 (CA125), which is a membrane glycoprotein belonging to the mucin family and secreted by 80% of the serous ovarian tumours. The aim of this study was to analyze the clinical relevance of a follow-up of CA125 kinetics of five ovarian carcinoma patients at advanced stages and under neoadjuvant chemotherapy. CA125 was assayed on a Kryptor(®) (Thermo-Fisher BRAHMS) and CA125 kinetics on semi-logarithmic curve with the software "Cinetic System". This software calculates the half-life and the doubling time between two points and can detect a line of tendency. It can also point out the nadir value. Kinetics are followed during 1 or 2 years. For all patients, we observe a very good agreement between kinetics, clinical and radiological issues (tumor size reduction). For three patients, after the first chemotherapy, the lines of tendency are decreasing. In one case with peritoneal carcinomatosis, the retrospective study of the pattern showed a biphasic curve anticipating the radiological modifications. For the two other patients, the normalisation of the CA125 is never obtained with no possible surgery. A greatest study could confirm the interest of associating this graphic approach to the clinical and radiological elements in order to optimize the medico-surgical assumption of responsibility of these patients with ovarian carcinoma at advanced stages, under first adjuvant treatment.

[Importance of hemolysis on neuron-specific enolase measurement]. / Importance de l'hémolyse sur le dosage de l'énolase neurospécifique (NSE).

The aim of this work is to establish a pre-analytical approach suitable for the neuron-specific enolase (NSE) measurement. This enzyme which is synthesized by neurons and neuroendocrine cells, is a marker useful for the diagnosis and the monitoring of patients with neuroendocrine tumors (neuroblastoma, small cell lung cancer) and during stroke to assess neuronal damage. This NSE measurement is very sensitive to hemolysis due to the abundance of the enzyme in red blood cells. Two methods of evaluation of hemolysis have been compared: the determination of free haemoglobin (Hb) by spectrophotometry and the indirect measurement of an hemolytic index with a multiparameter analyzer, the Modular (Roche Diagnostics). The correlation between these 2 methods on 42 samples is very satisfactory: Y (free Hb) = 12.337 X (index) + 31.743 r = 0.997. The NSE assay is based on TRACE (Time Resolved Amplified Cryptate Emission) technology, on a Kryptor (BRAHMS). The influence of hemolysis on the determination of NSE was confirmed by overloading with hemoglobin (hemolysate) 3 pools of serum with NSE concentrations close to the threeshold decision. The determination of NSE shows an increase in concentration parallely to the hemolytic index (about 150% for an hemolytic index of 10). Consequently, in our laboratory the NSE determination is realized only for samples presenting an hemolytic index < or = 10, this allowing a good monitoring of kinetics of this marker.